Ionic mechanisms involved in muscarinic regulation of neuronal and paraneuronal activity

The characteristics of neuronal and paraneuronal muscarinic inhibition and excitation were analyzed using rat caudate nucleus (CN) slices and isolated chromaffin cells obtained from the rat adrenal medulla. In CN neurons, either acetylcholine (ACh), carbachol, or muscarine inhibited orthodromically activated firing, while nicotine had no effect on neuronal activity. Muscarine decreased the amplitude of EPSPs without altering the resting membrane potential (RMP), input impedance and EPSP time courses. These results indicate that muscarinic receptors produce the presynaptic inhibition of synaptic transmission in the CN. In adrenal chromaffin cells, it was found that ACh, muscarine, and nicotine all increased extracellularly recorded firing. During voltage clamp recording at the RMP, ACh induced a transient inward current (fast response) followed by a long-lasting current (slow response). Muscarine induced the slow response, whereas nicotine induced the fast response. Muscarine reduced the inward K+ current produced by the application of a high K+ medium to cells. During patch clamp recording, muscarine decreased the opening rate of the single K+ channels. These results indicate that the muscarinic excitation of adrenal chromaffin cells was triggered by a reduction in the number of active K+ channels at the RMP.